The declining rate of residual renal function, expressed by residual creatinine clearance (RCcr), was compared among 7 patients treated with 2 times a week hemodialysis (HD) (Group 1) and 8 patients with 3 times a week HD (Group 2). The RCcr in Group 1 declined linearly from 8.85±1.79ml/min (M±SE) at the beginning of HD to 2.14±0.25ml/min at the time when HD was changed to 3 times a week. The average time during which 2 times a week HD was performed was 3.56±0.47 years, ranging from 1.75 to 5.67. The regression line of RCcr in Group 2 consisted of 2 different slopes first a steep slope followed by a less steep slope. The rate of decline of RCcr in Group 1 was 0.141±0.029ml/min/month, being significantly lower than the 0.651±0.077 obtained from the first slope in Group 2 (p<0.001). The RCcr at the initiation of HD in Group 1 was 8.85±1.79ml/min, being higher than the 4.45±0.47 in Group 2, but this difference was not statistically significant.
It is concluded that earlier but less frequent HD treatment can preserve the RCcr longer.

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To elucidate the pathogenesis and progression of uremic neuropathy, free myoinositol concentration and the rate of ³²P incorporation into inositol phospholipids were measured in the peripheral nerves of rats with chronic renal failure. At 1, 7 and 20 weeks after the induction of uremic status, peripheral nerve conduction velocities were lowered with the elevation of BUN and serum creatinine levels. Although plasma myoinositol level of uremic rats was elevated three-to four-fold over the normal level in our parallel study, free myoinositol concentration in the sciatic nerve at 1, 7 and 20 weeks after the induction of uremic status were 1.76±1.23, 1.22±0.76 and 0.52±0.42nmol/mg wet weight, respectively, and there was little change compared with those of the controls (1.94±0.30, 1.63±0.76 and 0.59±0.13nmol/mg wet weight, respectively). The ³²P incorporation rate into inositol phospholipids as well as that into other phospholipids in the sciatic nerve was not significantly altered. These results indicate that the pathogenesis and progression of uremic neuropathy is not related to the inositol phospholipid metabolism and is differed from that of diabetic neuropathy.

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Various studies have been made on the effect of a dialysate with a low concentration of Mg (low-Mg dialysate) in short-term use. However, there have been few reports on the effect of a low-Mg dialysate in long-term use. Therefore, a study was conducted on 27 hemodialysis patients whose disease was stable. In this study, the concentration of Mg in the dialysate was lowered from the 1.5mEq/l used before the study to 0.5mEq/l, and hemodialysis was performed at this Mg concentration for 14 months. The effect of the low-Mg dialysate on the blood composition was then studied by analyzing the serum levels of Mg, Ca, P and the c-terminal of parathyroid hormone (c-PTH) before and after dialysis.
The serum Mg level, which was 2.53±0.28mEq/l prior to the change in the Mg level, decreased to 1.89±0.25mEq/l 14 months after the change (p<0.001). The number of patients showing a normal Mg level (0.66-2.30mEq/l) thus increased. In no cases was hypomagnesemia observed after dialysis. In comparison with the level observed before the change, a significant decrease was seen in the serum Ca level (p<0.05) in the first month and in the serum P level (p<0.05) in the fifth month after the change. No significant changes were seen in these levels in other months. There was no significant difference between the serum c-PTH levels determined before and after the change to the low-Mg dialysate.
The long-term use of the low-Mg dialysate (0.5mEq/l) was found to be capable of treating hypermagnesemia without causing hypomagnesemia. It was also possible to prevent an increase in the serum c-PTH level by controlling the serum Ca at a proper level. In addition, this regimen resulted in a slight reduction of itching in the patients. Thus, long-term use of the low-Mg dialysate is thought to have utility.

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Nineteen patients with chronic renal failure were examined and classified into three groups: 5 without hemodialysis (HD), 9 with long-term HD and hematocrit (Hct) from 20 to 29% (renal anemia), and 5 with long-term HD and Hct over 40% (normal Hct). In these three groups, the pathogenesis of anemia was studied by assessing the effects of patient's and normal sera on the proliferation into colonies in vitro of the erythroid progenitor cells (BFU-E and CFU-E) in human bone marrow. CFU-E and BFU-E were not inhibited by the sera of either predialysis or normal Hct patients, but they were inhibited when the autologous sera of renal anemia patients were incubated with normal human bone marrow cells. They were not inhibited when normal sera were incubated with bone marrow cells of renal-anemia patients. CFU-E and BFU-E were positively correlated with hemoglobin and Hct, and were negatively correlated with BUN, creatinine and ribonuclease. The erythropoietin levels in most of the patients were within normal range, and were not correlated with CFU-E. Ribonuclease was signifificantly higher in renal anemia patients than in normal Hct patients.
It is concluded that erythroid progenitor cells in HD patients are intact, and the severity of renal anemia may be determined by numerous inhibitors of erythropoiesis. Some of the inhibitors can be dialyzed.

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Changes in dialysis efficiencies were studied in patients with chronic renal failure undergoing CAPD. The subjects consisted of 11 diabetic and 6 non-diabetic patients.
The amount of fluid removal per dialysate exchange and the D/P ratios of urea nitrogen and creatinine were used as ability indexes of ultrafiltration and mass transfer, respectively. Those parameters were compared between diabetic and non-diabetic patients at 12-month intervals. The efficiency of solute transport was well maintained throughout the observation period in both groups. The ultrafiltration tended to be diminished after 12-month CAPD treatment (7.3% decrease for diabetic and 12.3% decrease for non-diabetic patients). These differences, however, were not statistically significant. In two of the patients there were substantial declines in ultrafiltration. One was diabetic and the other was non-diabetic. In both cases a peritoneal sclerosis resulting from recurrent peritonitis appeared to be the cause of the diminished ultrafiltration.
We conclude that the presence of diabetes mellitus has little influence on peritoneal function during CAPD and that peritoneal sclerosis seems to be an important cause of impairment in peritoneal function.

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Despite advances in the treatment of systemic lupus erythematosus (SLE), renal failure still develops in patients with SLE. Among patients on hemodialysis (HD), cases with SLE are increasing.
This study revealed that intensive immunosuppressive therapy and early HD therapy are indicated for patients with rapidly deteriorating renal function associated with active SLE. The study was conducted on 18 patients with SLE who were on HD therapy in our hospital between 1975 and 1986. These cases were divided into 3 groups; Group A: Cases dying within 2 months after being put on HD (n=4). Group B: Cases with long-term maintenance HD (n=10). Group C: Cases with substantial recovery of renal function allowing for cessation of HD therapy (n=4). In group A, the patients received HD therapy as a result of acute exacerbation by complications such as cerebral bleeding and infection. The causes of death were directly attributable to SLE activity. These lethal complications resulted from active SLE and high dosages of predonine. In group B, SLE was in the “burn out” state, and the dosage of predonine was low at the time patients were put on HD. After HD therapy, there was no SLE relapse in these patients. In group C, overhydration, heavy proteinuria or increased SLE activity led to HD therapy. These patients showed substantial recovery of renal function and they no longer needed HD after 18-55 days. Early introduction to HD and highdose predonine eliminated debilitating disruptive factors. Two out of four patients were put back on HD after 18 and 46 months, because of gradual decrease in renal function without complications.
Intensive immunosuppresive therapy for several weeks is indicated for patients with severely and rapidly impaired renal fuction associated with active SLE. But, in SLE patients with end stage renal function, overhydration, hypertension and infection were lethal complications. Because it is important to prevent these complications we advocate early HD therapy to control hypertension and overhydration.

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Serial alterations of peripheral blood lymphocyte subpopulations and mitogen responses of lymphocytes during hemodialysis were studied to clarify the effects of hemodialysis on immune responses in vivo. Twenty patients undergoing hemodialysis treatment were subjected to our study. Four kinds of dialyzer membranes, cuprophane, cellulose acetate, PMMA (polymethyl methacrylate) and EVAL (ethylene vinyl alcohol), were used during the hemodialysis treatment. The results obtained were as follows: 1) Absolute counts of the lymphocytes were significantly decreased at 15min after the start of hemodialysis when the cellulose acetate membrane was used (p<0.05). 2) Percentages of OKT3 positive cells were significantly increased at 15min after the start of hemodialysis when the PMMA membrane was used (p<0.05), while none of the four membranes was found to have affected the OKT4/OKT8 ratio or OKB1 positive cells. 3) Percentages of OKM1 positive cells were significantly decreased at 15min after the start of hemodialysis when the cuprophane membrane was used (p<0.05). 4) Proliferative responses of the lymphocytes to PHA were significantly enhanced at 15min after the start of hemodialysis compared with those before hemodialysis when the cuprophane membrane was used (p<0.05), while they were not significantly enhanced when other membranes were used, although individual cases showed remarkable enhancement. 5) Comparison of the normal and low responders to PHA, revealed that the PHA responses of the lymphocytes in the low responder group particularly showed remarkable enhancement at 15min after the start of hemodialysis compared with those before hemodialysis (p<0.01). 6) In the low responder group, the decreased rate of OKM1 positive cells and the enhancement rate of PHA responses of the lymphocytes tended to be positively correlated, though this was not significant. From these results, it was suggested that the enhancement of the PHA responses of the lymphocytes at 15min after the start of hemodialysis was possibly caused by a decrease in suppressor monocytes.

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A total of 166 maintenance dialysis patients were separated among 4 groups according to the duration of their dialysis; Group A: more then 10, B: more then 5 and less than 10, C: more than 1 and less than 5 and D: less than 1 year. Renal osteodystrophy (ROD) in those patients was observed periodically by microdensitometry, and the bone index (BI) was calculated based upon metacarpal index and bone mineral content thus obtained. In addition, the plasma levels of aluminum were measured prior to and after administration of desferrioxamine, intact PTH (i-PTH), active vitamin D₃ and other treatment.
As the duration of dialysis increased, the BI worsened. Compared to groups A and B, group C demonstrated a sinilarly rapid progress in ROD in 5 years. The level of active vitamin D₃ was low in all 4 groups. The i-PTH, though normal in group C, tended to increase linearly with the duration of dialysis. Aluminum in plasma was high even in the initial phase and the degree of increase in aluminum with the infusion of desferrioxamine was positively correlated with the duration of dialysis.
Based upon these observations, it is concluded that osteomalacia exists even in the initial phase due to deficiency of active vitamin D₃ and to the aluminum accumulation and that prolonged dialysis also causes osteitis fibrosa and gradually increased i-PTH.

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We investigated the pharmacokinetics of Cefoperazone (CPZ) in 10 patients with routine hemodialysis. At the beginning of the hemodialysis, 1g of CPZ was injected intravenously on the dialysis day and, later, on the non-dialysis day at intervals of three dialysises. The patients were hemodialyzed for 5 hours with blood flow rates of 150ml/min and dialysate flow rates of 500ml/min. One patient (case 1) was treated with hemofiltration and one (case 10) had chronic hepatitis. The serum concentration of CPZ was measured by bioassy. The data obtained were analyzed by the two-compartment-theory.
During the dialysis, the serum concentration of CPZ was 122±42μg/ml after 15 minutes, 74.2±31μg/ml after 1 hour, 39.5±12μg/ml after 2 hours, 21.3±8μg/ml after 4 hours, 15.1±6μg/ml after 5 hours, and less than 1.56μg/ml 24 hours later. The difference between the concentrations of CPZ at the inlet and at the outlet of the dialyzer was not statistically significant. On the non-dialysis day, the serum concentration of CPZ was 120±45μg/ml after 15 minutes, 51.2±17μg/ml after 2 hours, 22.5±8μg/ml after 5 hours, and these data were not significantly different from those on the dialysis day. According to the analysis with the two-compartment-theory, C_max was 171μg/ml, Kel was 0.88hr^-1, T_1/2 was 2.13 hours. The T_1/2 of the patient treated with hemofiltration (case 1) was 2.45 hours. T_1/2 more than 4 hours were noticed in one case with liver dysfunction (case 10) and two of nine cases without liver dysfunction (case 5, 7).
In conclusion, CPZ may be administered safely without a change of dose or interval of the drug to most of the patients with normal liver function on routine hemodialysis.

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To investigate the role of Al on anemia in hemodialysis patients, we measured serum Al concentrations (serum-Al) and the Al content in red blood cell (RBC-Al) from 10 normal subjects and 27 hemodialysis patients, using flameless atomic absorption spectrophotometry. The serum-Al and RBC-Al in hemodialysis patients were significantly higher than the controls (p<0.001). There was a significant positive correlation between serum-Al and RBC-Al in hemodialysis patients (r=0.687, p<0.001). There was also a negative correlation between RBC-AI and Hb (r=-0.506, p<0.01), Ht (r=-0.473, p<0.02) or MCH (r=-0.439, p<0.05). It is suggested that the accumulation of Al may play a role in the development of anemia in hemodialysis patients.

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